This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this study is to examine a possible relationship between agents, other than nicotine present in cigarettes and overall drug dependence in smokers and non-smokers. Nicotine dependence is a complex biological and behavioral problem that can be extremely difficult to overcome. An improved overall understanding of drug dependence, coupled with the identification of nicotine as a drug with dependence potential, has been instrumental in the development of medications and behavioral treatments for nicotine dependence. Researchers are beginning to find out that there may be chemical ingredients other than nicotine in cigarette smoke that contribute to tobacco's addicting potential. Two classes of compounds, tetrahydroisoquinolines (TIQ) and beta-carbolines, have been found to be involved brain mechanisms that may advance to drug dependence. Of primary importance, there are compounds may help regulate feelings of pleasure, or "reward pathways". Both of these compounds (TIQ and b-carboline) might be responsible in nicotine seeking behavior and dependence. This study will evaluate statistically the inter- and intra-individual variability in the TIQ and b-carbolines, as well as the smoking history/nicotine dependence scores of nonsmokers, light smokers, and heavy smokers. This study will recruit sixty healthy young volunteers (20 nonsmokers, 20 light smokers, and 20 heavy smokers). Subjects will be given information regarding the study and will provide informed consent. Upon enrollment, subjects will supply blood samples for measurement of baseline levels of TIQ and b-carboline levels. An evaluation of smoking history and nicotine dependence score will be used to correlate smoking dependence with the level of these compounds. Subjects will return to the GCRC for a second visit with blood and urine tests repeated to ensure accuracy. If this research shows that a relationship does exist, more detailed interventions will be designed that assess the suitablilty of these compounds as possible biomarkers of nicotine dependence.